Pulmonary Eosinophilic Histiocytosis
Introduction
Introduction to pulmonary eosinophilic histiocytosis Pulmonary eosinophilic histiocytosis: previously included in histiocytosis X (HX), Langerhans cell mytiocytosis (LCH) is currently considered more appropriate, as recent studies have shown this group of diseases The main lesion is clonal hyperplasia of Langerhans tissue cells, which is characterized by disseminated acute lesions in infants (Letter-Siwe disease), chronic multifocal lesions (Hand-Schuller-Christian), and slow-moving focal lesions Acid cell granuloma). Lung LCH can be part of a multisystem lesion or limited to the lung (eosinophilic granuloma, primary lung LCH). Primary lung LCH is a rare smoking-related interstitial lung disease, mainly occurring in young adults, and rare cases are also isolated osteolytic lesions; more rarely, multifocal or extensive dissemination Sexual lesions, similar to the pediatric Letter-Siwe disease. Progressive lesions are similar to IPF; however, this disease is generally a benign and prolonged clinical course, although LCH has some similarities with other diffuse interstitial lung diseases, but as an independent disease, it has a different disease than other diseases. Clinical, radiological and pathological findings. basic knowledge The proportion of sickness: 0.002%-0.003% Susceptible people: more common in adults Mode of infection: viral infection Complications: pneumothorax
Cause
Causes of pulmonary eosinophilic histiocytosis
Causes:
An allergic disease of unknown etiology may also be a viral infectious disease.
Pathogenesis:
The pathogenesis of LCH is unclear, but the fact that almost all have a history of smoking suggests that smoking may be the cause. A hypothesis of the pathogenesis of this disease (the bell peptide hypothesis) suggests that the increase in the production of bombesin-like peptides plays an important role in the bombesin peptide. Is a neuropeptide produced by neuroendocrine cells. This cell is increased in the lungs of smokers. The bell peptide peptide can chemotaxis of monocytes, promote epithelial and fibroblast mitosis, and stimulate cytokine production. Significant features support the hypothesis that these peptides play a role in inflammation and fibrosis in LCH, and that tobacco glycoproteins and other regulatory glycopeptides (such as granulocyte-macrophage colony-stimulating factor GM-CSF) may be involved in the pathogenesis of LCH Play a potentially important role.
Recent research has focused on the regulation of white blood cell migration.
Studies have shown that the pathogenesis of LCH includes regulation of changes in the expression of adhesion molecules between leukocytes and endothelial cells, and plays an important role in neutrophils. The adhesion molecule expressed by endothelial cells is intercellular adhesion molecule-1 (ICAM-1), LCH. Langerhans cells can express ICAM-1 in the patient's lung biopsy specimens. Interestingly, other leukocyte adhesion molecules, such as 1 and 2 integrin, are also expressed. The significance of these changes and their correlation with LCH need to be further elaborated.
In addition, studies have suggested that viral infection can be a potential cause of systemic LCH, but no evidence of reliable service suggests that viral infection plays a role in LCH.
Abnormal immune function was also observed in lung LCH, which was characterized by non-specific increase in IgG in BALF, circulatory and tissue-affinity immune complexes, and abnormal T cell function, which may be important in the pathophysiology of the disease. Alterations may also represent only systemic immune effector cell activation.
Although this disease is not a monoclonal disease, it is often associated with lymphoma and suggests a relationship with malignant tumors. Currently, there is reason to believe that lung HX may be a precancerous lesion (Figure 1).
LCH early inflammatory lesions centered on bronchioles, containing eosinophils, lymphocytes and neutrophils. In fact, LCH is not a granulomatous disease, and the lesions lack eosinophils, so the old name "eosinophils" Granuloma is not suitable. Lesions often involve pulmonary arterioles and venules, so it is often described as "distribution along the bronchial vessels." LCH vascular involvement is common, but until recently it was quantitatively evaluated. Travis noted 80% of biopsy specimens. There is vascular involvement, and there are also common desquamative interstitial pneumonia (in the lung parenchyma filled with alveolar macrophages between Langerhans cells) and respiratory (smoker) bronchiolitis (the bronchial cavity and surrounding air cavity are full of pigmented Macrophages); in addition, intracavitary fibrosis was found to be common (80%), characterized by wall integration, alveolar occlusion and intraluminal sprouting, of which 59% were mild and 20% were moderate, only 9% is severe, and these findings support the hypothesis that intraluminal fibrosis is a mechanism of alveolar collapse and progresses to pulmonary fibrosis and lung remodeling.
Interstitial fibrosis and small cyst formation, Ueno predominance, occurs in the progression of the disease; and, the distribution of the Ueno is different from IPF, the latter lesions are more common in the lower field, the further development of the lesion can affect the lung parenchyma around the bronchi The so-called "stellate lesions" produce a characteristic change of the disease.
The relatively old diseased cells have relatively few components, which produce diffuse interstitial pathological changes, which are difficult to distinguish from other end-stage pulmonary fibrosis. The mechanism of cyst formation is still unclear, probably due to the necrosis of the old stellate lesions; This may be due to secondary inflammatory lesions in the distal end of the bronchial vasculopathy relative to the avascular region; these cystic formations are ultimately associated with proximal airway obstruction caused by stellate lesions.
The LCH pathological cell type is Langerhans cells, which are differentiated from mononuclear-macrophage cell lines. Langerhans cells are normally found in the skin, the reticuloendothelial system, the lungs and the pleura, and their cytoplasm is lightly stained, with large nucleoli, electron microscopy. Typical five-layered cytoplasmic inclusion bodies or Birbeck particles (X bodies) can be seen. Although this cell can also be found in healthy smokers and other lung lesions (such as IPF) or normal lungs, it is indeed a characteristic of LCH. The Langerhans cell population appeared and was significantly more numerous than other lung lesions, but a quantitative specification for LCH diagnosis has not been established.
Prevention
Pulmonary eosinophilic histiocytosis prevention
Because smoking is closely related to lung histiocytosis, such patients should do their utmost to discourage patients from quitting. Thoracic closed drainage or pleural sclerotherapy can be performed, but pleural sclerotherapy should be avoided in patients who will undergo lung transplantation.
Lung transplantation may be considered in patients with advanced lung histiocytosis and severe pulmonary hypertension, but some patients may have lung histiocytosis after lung transplantation, accompanied by severe deterioration of lung function. The impact of the rate is not yet confirmed.
Complication
Pulmonary eosinophilic histiocytosis complications Complications
Often complicated by pneumothorax and co-infection (such as Aspergillus) or tumor.
Symptom
Pulmonary eosinophilic histiocytosis symptoms common symptoms dyspnea fever, asthma, dry cough, blood fatigue
LCH clinical manifestations are diverse: some have a chest X-ray due to pneumothorax, or respiratory and systemic symptoms, and patients often show dry cough (50% to 70%), difficulty breathing (40%), chest pain (10% to 21%), fatigue (30%), weight loss (20% to 30%), and fever (15%), 50% of patients have a history of rhinitis.
25% of patients may have repeated pleural pain and spontaneous pneumothorax. In the absence of pneumothorax, pleural thickening and effusion are rare. Occasionally, hemoptysis (13%) is reported. At this time, it should be noted whether there is a combined infection (such as Aspergillus) or Tumor.
4% to 20% of patients may have bone cystic lesions, and local pain or pathological fractures. Because the comprehensive bone examination is not routine, the exact number of patients with bone damage is still unclear. The symptoms of bone involvement can be typical. Before the lung symptoms appear, it can also be the only manifestation of LCH. The imaging findings are not diagnostic. In most cases, the bone damage is single, and mainly involves the flat bone.
Central nervous system involvement is characterized by a diabetes insipidus accounted for 15%, which is generally considered to indicate a poor prognosis.
Physical examination is often not obvious, bursting sounds and clubbing (toe) are not common, secondary pulmonary hypertension can occur; pulmonary heart disease can be seen in the advanced stage, routine laboratory tests are often meaningless, and peripheral blood eosinophils The count is normal.
Medical history and physical examination are the first steps in the diagnosis of suspected lung LCH patients. Unfortunately, their symptoms and signs are often non-specific, and often suggest other more common lung lesions, such as 50-year-old smokers who have asthma and cough. And breathing difficulties, COPD is more common than LCH; however, when repeated pneumothorax, diabetes insipidus and bone pain occur, it is helpful for diagnosis. The history of smoking is common, but it is not a necessary history, because LCH is indeed visible in non-smoking. patient.
Most patients with LCH are evaluated after chest imaging abnormalities. For example, CT findings are of diagnostic significance. Therefore, CT examination should be performed on suspected patients. For all suspected LCH diffuse ILD, it is recommended before biopsy. HRCT examination, obvious CT features and appropriate clinical background data can be exempted from histological confirmation, but it is worth noting that LCH chest CT is often atypical, so it needs to be associated with lymphangioleiomyomatosis, tuberous sclerosis. , allergic alveolitis, sarcoidosis and IPF image confusion, in this case should be further diagnosed.
BAL has diagnostic value for suspected LCH, the total number of cells increases (same as smokers); common neutral and eosinophils increase slightly; the total number of lymphocytes in active lesions can also increase, and the CD4/CD8 ratio decreases; BALF Langerhans cells can be identified by special staining for S-100 protein or peanut agglutinin. These cells are OKT-6 (CD-1) positive and can be recognized by specific monoclonal antibody (MT-1); characteristic under electron microscope Birbeck or pentad body, there is no definitive diagnostic criteria for LCH based on the number of Langerhans cells in BALF. Langerhans cells can also be found in other BALF cell fractions (now smokers, other ILD or bronchioloalveolar carcinoma) ), even in normal people, so only the Langerhans cell diagnosis is insufficient.
In order to obtain histological evidence, TBLB is sufficient to confirm the diagnosis. Mistakes and lack of tissue are the main causes of false negative or no diagnostic value. Thoracic lung biopsy is more effective under thoracic or TV guidance and the risk factors for surgery are also It was reduced to the lowest level. In the difficult case, immunostaining with monoclonal antibody CD-1 (OKT-6) was used to distinguish Langerhans cells from other tissue cells, which was helpful for diagnosis.
Examine
Examination of pulmonary eosinophilic histiocytosis
Routine laboratory tests for eosinophil counts are meaningless and the peripheral blood eosinophil counts are normal.
1. Although the chest X-ray is not diagnostic, it is very characteristic. If there are unclear nodule shadows (2~10mm), reticular nodules, upper sac cystic or honeycomb lung, lung volume is not The combination of changes in the rib angle and the rib angle is highly specific for the diagnosis of this disease. Typical reticular nodules are seen in the middle and upper body. Consistent with the pathological results, the total amount of lungs is normal, but lung hyperinflation and Lung volume is reduced, except for LCH, lymphoproliferative disease, tuberous sclerosis, chronic allergic lung (bubbles), stage III sarcoidosis, constrictive bronchiolitis, and any ILD with emphysema Can be expressed as an increase in lung volume.
LCH imaging markers are small cysts and nodules, occasionally miliary lesions, LCH lung or mediastinal lymph nodes are rare, if the second diagnosis of swelling should consider malignant tumors, the primary pleural involvement of the disease Rarely, pleural hypertrophy is often caused by the treatment of pneumothorax. Bone damage can occur in any bone, including ribs. In rare cases, the patient only presents as an isolated pulmonary nodule and is confirmed to be LCH in a biopsy.
2. CT examination of the chest: When a young smoker has multiple characteristics of multiple cysts and nodules in the mid-Ueno field, it can be considered to diagnose LCH. The boundary of small nodules can be clear or unclear, occasionally It can be large and singular, and the cellular lung changes in the advanced stage.
A series of CT scans can be observed that the degree of cyst formation is often underestimated on conventional X-rays during a period of time when the nodule undergoes cavitation and progresses toward cystic progression, which can be explained in the literature before the routine application of thin-layer CT. Many of the so-called "natural relief" cases.
3. Magnetic Resonance (MRI) examination: MRI in LCH applications is limited to assessing bone and CNS lesions.
4. Pulmonary function tests: LCH patients can show various forms of lung function changes, including normal, obstructive, restrictive or mixed. In general, the total amount of lungs is constant and the airflow is almost normal; the common diffusing function is disproportionate. Decreased ground, suggesting pulmonary vascular involvement; a small number of patients with airflow limitation, and sometimes associated with increased airway responsiveness, can be significantly improved after bronchodilator treatment, when the increase in airway responsiveness may reflect The coexistence of COPD is not common in LCH with typical asthma manifestations.
In the 23 cases of LCH reviewed by Craussman et al, there were two major subgroups of lung function changes. The first group showed normal lung volume, normal or near normal airflow. The elastic retraction force of this group of patients was normal after lung mechanical measurement. The second group showed mainly restrictive lesions, the total amount of lung decreased and the elastic retraction force increased. Both of the diffuse functions were significantly reduced, and the restrictive lesion group often showed a longer course.
The average AaDO2 gradient was normal in the two subgroups at rest. However, 5 patients with severe disease had significantly increased AaDO2 and needed oxygen therapy. The pH and PaCO2 were normal at rest, so the arterial blood gas was at rest. The assessment is very insensitive.
5. Exercise test: clinically, LCH patients usually show limited mobility and decreased exercise endurance, and are not proportional to lung function abnormalities. In the cross-sectional study of 23 cases of LCH, it is found that the work or exercise is extremely oxygen-consuming. The exercise capacity of the quantity (VO2) was significantly reduced, which was 54±4% and 44±3% of the predicted value respectively; the oxygen output per stroke decreased to 56±3% during the extreme exercise, and the anaerobic domain decreased to VO2 max. The value of 33±1%, the maximum ventilation response (VE max, 83±5%) exceeded the maximum work level, the maximum ventilation response was not limited, and the VE was far below the expected ventilation limit, and the gas exchange anomaly was manifested in AaDO2 increases as the movement increases.
VD/VT, which reflects pulmonary vascular function, is abnormally elevated or not decreased in most patients, suggesting that the pulmonary blood vessels are involved in pathological or functional pathology.
Studies have shown that the decline in exercise tolerance in LCH patients is caused by mechanical factors and pulmonary vascular involvement.
Diagnosis
Diagnosis and identification of pulmonary eosinophilic histiocytosis
In the presence of extensive fibrotic progressive lesions, Langerhans cells in tissue specimens and BALF are significantly reduced, making diagnosis difficult. In most cases, combined with TBLB, BALF analysis, supplemented with tissue and BALF, CD-1 positive cells are often sufficient Get a correct diagnosis.
The disease was first differentiated from pulmonary nodular disease with diffuse nodular type, and secondly with idiopathic pulmonary interstitial fibrosis, chronic exogenous allergic alveolitis and diffuse alveolar cell carcinoma.
